Laxative treatment elevates plasma homocysteine: a study on a population-based Swedish sample of old people

Objectives Elevated plasma homocysteine might indicate an increased risk of cancer, and cardiovascular and neurological diseases. The homocysteine level depends on the supply of folate and cobalamine, and constipation and/or laxative treatment might compromise this supply. The present study examined the impact of constipation and laxative treatment on the blood levels of homocysteine, folate and cobalamine in a population-based sample of aged people, including consideration of frailty and impaired renal function, both of which may also influence the homocysteine level.Methods The study was based on biochemical tests in 341 females and 183 males aged 82 years or older. The concentrations of homocysteine (plasma), folate, cobalamine and urea (serum) were measured in subjects with and without ongoing treatment with laxative drugs. Values were adjusted for age, gender and frailty, as well as for clinical diagnoses and drug therapies known to affect homocysteine levels.Results Homocysteine levels were increased and those of folate reduced in aged subjects on laxatives. Homocysteine remained elevated after adjusting for frailty and various neurological disorders. There was no significant effect on homocysteine and folate in constipated subjects without laxatives.     

Drug history overrides opioid reinforcement in a rat runway procedure

To determine the effect of the drug history of rats on their subsequent operant behaviour in the rat runway procedure, we tested the mu opioid receptor agonists morphine and remifentanil and found a carryover of previous drug/saline experience that was not found for a food reinforcer. Previous exposure to saline significantly decreased the apparent reinforcing effect of subsequently offered morphine or remifentanil, while previous experience with morphine or remifentanil significantly increased responding for saline. This carryover of a previous learning experience on subsequent operant performance in the rat runway procedure cautions that the drug history should be considered and might even invalidate subsequent findings when testing drugs of abuse or other reinforcers.     

Pilot study on the effect of parenteral vitamin E on ischemia and reperfusion induced liver injury: a double blind, randomized, placebo-controlled trial

BACKGROUND AND AIMS: Liver surgery usually involves ischemia and reperfusion (I/R) which results in oxidative stress and cell damage. The administration of antioxidants should diminish or prevent this damage. The purpose of this study was to investigate the effect of the antioxidant vitamin E on I/R injury. METHODS: We carried out a placebo-controlled double-blind study on 68 patients undergoing elective, tumor-related, partial liver resection. 47 patients were qualified for the per protocol population based evaluation. The patients were randomly assigned to two groups. The day before surgery one group received three infusions containing vitamin E (600 IU=540 mg vitamin E emulsion). The other group received three infusions of placebo. RESULTS: Length of stay in the intensive care unit (ICU) was significantly shorter in the verum group than in the placebo group (P<0.05). There were signs of improvement for AUC AST (P<0.05), ALT and GLDH in the verum group after surgery. Serum vitamin E concentration increased after administration of vitamin E infusion and declined in both treatment groups after surgery (P<0.01). In the verum group vitamin E deficiency was prevented while vitamin E concentration remained low in the placebo group (P<0.01). CONCLUSIONS: The findings from this study indicate that preoperative administration of vitamin E is safe and that this treatment may have beneficial effects by reducing the impact of I/R injury in liver surgery.     

Plasmids encoding membrane-bound IL-4 or IL-12 strongly costimulate DNA vaccination against carcinoembryonic antigen (CEA)

Vaccination with plasmids encoding an antigen of interest (DNA vaccination) is a new strategy to achieve effective immunization against many agents. DNA vaccination can be ameliorated by co-administration of plasmids encoding a cytokine. Thus far, only plasmids encoding soluble cytokines have been used for this purpose. However, these plasmids can induce release of cytokines into the circulation and could potentially cause many undesirable effects. We undertook this study to determine whether membrane-bound cytokines, which would restrict their localization at the site of administration, can act as immunoadjuvants. We and others have previously shown that plasmids encoding soluble IL-4 and IL-12 are effective adjuvants for DNA vaccination. In this study, we demonstrate that DNA co-vaccination with membrane-bound IL-4 (mbIL-4) or membrane-bound IL-12 (mbIL-12) both enhance anti-CEA immunity, as detected by in vitro and in vivo assays. Mice co-injected with plasmids encoding CEA and either type of membrane-bound cytokine rejected transplanted CEA-positive tumor cells strongly. Notably, unlike secreted IL-4, mbIL-4 was the most effective adjuvant for anti-tumor immunity. This study demonstrates that membrane-bound cytokines are suitable adjuvants for DNA vaccination.     

Using the area under the curve to reduce measurement error in predicting young adult blood pressure from childhood measures

Tracking correlations of blood pressure, particularly childhood measures, may be attenuated by within-person variability. Combining multiple measurements can reduce this error substantially. The area under the curve (AUC) computed from longitudinal growth curve models can be used to improve the prediction of young adult blood pressure from childhood measures. Quadratic random-effects models over unequally spaced repeated measures were used to compute the area under the curve separately within the age periods 5-14 and 20-34 years in the Bogalusa Heart Study. This method adjusts for the uneven age distribution and captures the underlying or average blood pressure, leading to improved estimates of correlation and risk prediction. Tracking correlations were computed by race and gender, and were approximately 0.6 for systolic, 0.5-0.6 for K4 diastolic, and 0.4-0.6 for K5 diastolic blood pressure. The AUC can also be used to regress young adult blood pressure on childhood blood pressure and childhood and young adult body mass index (BMI). In these data, while childhood blood pressure and young adult BMI were generally directly predictive of young adult blood pressure, childhood BMI was negatively correlated with young adult blood pressure when childhood blood pressure was in the model. In addition, racial differences in young adult blood pressure were reduced, but not eliminated, after controlling for childhood blood pressure, childhood BMI, and young adult BMI, suggesting that other genetic or lifestyle factors contribute to this difference.     

Test bias in a cognitive test: differential item functioning in the CASI

Assessment of test bias is important to establish the construct validity of tests. Assessment of differential item functioning (DIF) is an important first step in this process. DIF is present when examinees from different groups have differing probabilities of success on an item, after controlling for overall ability level. Here, we present analysis of DIF in the Cognitive Assessment Screening Instrument (CASI) using data from a large cohort study of elderly adults. We developed an ordinal logistic regression modelling technique to assess test items for DIF. Estimates of cognitive ability were obtained in two ways based on responses to CASI items: using traditional CASI scoring according to the original test instructions as well as using item response theory (IRT) scoring. Several demographic characteristics were examined for potential DIF, including ethnicity and gender (entered into the model as dichotomous variables), and years of education and age (entered as continuous variables). We found that a disappointingly large number of items had DIF with respect to at least one of these demographic variables. More items were found to have DIF with traditional CASI scoring than with IRT scoring. This study demonstrates a powerful technique for the evaluation of DIF in psychometric tests. The finding that so many CASI items had DIF suggests that previous findings of differences between groups in cognitive functioning as measured by the CASI may be due to biased test items rather than true differences between groups. The finding that IRT scoring diminished the impact of DIF is discussed. Some preliminary suggestions for how to deal with items found to have DIF in cognitive tests are made. The advantages of the DIF detection techniques we developed are discussed in relation to other techniques for the evaluation of DIF.